Abstract
Anthracyclines
are
chemotherapeutic
drugs
used
to
treat
solid
and
hematologic
malignancies.
However,
life‐threatening
cardiotoxicity,
with
cardiac
dilation
heart
failure,
is
a
drawback.
A
combination
of
in
vivo
for
single
cell/nucleus
RNA
sequencing
vitro
approaches
elucidate
the
underlying
mechanism.
Genetic
depletion
pharmacological
blocking
peptides
on
phosphatidylinositol
binding
clathrin
assembly
(PICALM)
evaluate
role
PICALM
doxorubicin‐induced
cardiotoxicity
vivo.
Human
tissue
samples
verification.
Patients
end‐stage
failure
chemotherapy‐induced
have
thinner
cell
membranes
compared
healthy
controls
do.
Using
mice
model,
it
possible
replicate
corresponding
phenotype
patients.
Cellular
changes
mice,
especially
cardiomyocytes,
identified
using
sequencing.
Picalm
expression
upregulated
only
cardiomyocytes
cardiotoxicity.
Amyloid
β‐peptide
production
also
increased
after
doxorubicin
treatment,
which
leads
greater
increase
membrane
permeability
cardiomyocytes.
reduce
generation
amyloid
β‐peptide.
This
alleviates
In
human
patients
,
elevated
as
well.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Авг. 23, 2024
Abstract
Alzheimer’s
disease
(AD)
stands
as
the
predominant
form
of
dementia,
presenting
significant
and
escalating
global
challenges.
Its
etiology
is
intricate
diverse,
stemming
from
a
combination
factors
such
aging,
genetics,
environment.
Our
current
understanding
AD
pathologies
involves
various
hypotheses,
cholinergic,
amyloid,
tau
protein,
inflammatory,
oxidative
stress,
metal
ion,
glutamate
excitotoxicity,
microbiota-gut-brain
axis,
abnormal
autophagy.
Nonetheless,
unraveling
interplay
among
these
pathological
aspects
pinpointing
primary
initiators
require
further
elucidation
validation.
In
past
decades,
most
clinical
drugs
have
been
discontinued
due
to
limited
effectiveness
or
adverse
effects.
Presently,
available
primarily
offer
symptomatic
relief
often
accompanied
by
undesirable
side
However,
recent
approvals
aducanumab
(
1
)
lecanemab
2
Food
Drug
Administration
(FDA)
present
potential
in
disrease-modifying
Nevertheless,
long-term
efficacy
safety
need
Consequently,
quest
for
safer
more
effective
persists
formidable
pressing
task.
This
review
discusses
pathogenesis,
advances
diagnostic
biomarkers,
latest
updates
trials,
emerging
technologies
drug
development.
We
highlight
progress
discovery
selective
inhibitors,
dual-target
allosteric
modulators,
covalent
proteolysis-targeting
chimeras
(PROTACs),
protein-protein
interaction
(PPI)
modulators.
goal
provide
insights
into
prospective
development
application
novel
drugs.
Molecular Neurodegeneration,
Год журнала:
2025,
Номер
20(1)
Опубликована: Янв. 27, 2025
Alzheimer's
disease
(AD)
is
among
the
most
devastating
neurodegenerative
disorders
with
limited
treatment
options.
Emerging
evidence
points
to
involvement
of
lipid
dysregulation
in
development
AD.
Nevertheless,
precise
lipidomic
landscape
and
mechanistic
roles
lipids
pathology
remain
poorly
understood.
This
review
aims
highlight
significance
lipidomics
lipid-targeting
approaches
diagnosis
We
summarized
connection
between
human
brain
AD
at
both
genetic
species
levels.
briefly
introduced
technologies
discussed
potential
challenges
areas
future
advancements
field
for
research.
To
elucidate
central
role
converging
multiple
pathological
aspects
AD,
we
reviewed
current
knowledge
on
interplay
major
features,
including
amyloid
beta,
tau,
neuroinflammation.
Finally,
assessed
progresses
obstacles
lipid-based
therapeutics
proposed
strategies
leveraging
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(25)
Опубликована: Март 6, 2023
The
accumulation
of
the
amyloid-β
peptides
(Aβ)
is
central
to
development
Alzheimer's
disease.
mechanism
by
which
Aβ
triggers
a
cascade
events
that
leads
dementia
topic
intense
investigation.
self-associates
into
series
complex
assemblies
with
different
structural
and
biophysical
properties.
It
interaction
these
oligomeric,
protofibril
fibrillar
lipid
membranes,
or
membrane
receptors,
results
in
permeability
loss
cellular
homeostasis,
key
event
disease
pathology.
can
have
an
array
impacts
on
reports
included:
carpeting
effect;
detergent
ion-channel
pore
formation.
Recent
advances
imaging
interactions
are
providing
clearer
picture
induced
disruption.
Understanding
relationship
between
structures
will
inform
therapeutics
targeting
cytotoxicity.
Annual Review of Biophysics,
Год журнала:
2024,
Номер
53(1), С. 455 - 486
Опубликована: Фев. 21, 2024
Cholesterol
has
been
conjectured
to
be
a
modulator
of
the
amyloid
cascade,
mechanism
that
produces
amyloid-β
(Aβ)
peptides
implicated
in
onset
Alzheimer's
disease.
We
propose
cholesterol
impacts
genesis
Aβ
not
through
direct
interaction
with
proteins
bilayer,
but
indirectly
by
inducing
liquid-ordered
phase
and
accompanying
liquid-liquid
separations,
which
partition
cascade
different
lipid
domains
ultimately
endocytotic
pathways.
explore
full
process
context
phases
induced
cholesterol,
including
protein
partitioning
into
domains,
mechanisms
endocytosis
experienced
secretases,
pH-controlled
activation
precursor
secretases
specific
environments.
Outstanding
questions
on
essential
role
are
identified
for
future
studies.
Ageing Research Reviews,
Год журнала:
2023,
Номер
90, С. 102026 - 102026
Опубликована: Июль 31, 2023
Since
the
discovery
of
mechanosensitive
Piezo1
channel
in
2010,
there
has
been
a
significant
amount
research
conducted
to
explore
its
regulatory
role
physiology
and
pathology
various
organ
systems.
Recently,
growing
body
compelling
evidence
emerged
linking
activity
health
disease
central
nervous
system.
However,
exact
mechanisms
underlying
these
associations
remain
inadequately
comprehended.
This
review
systematically
summarizes
current
on
implications
for
system
mechanobiology,
retrospects
results
demonstrating
cell
types
within
system,
including
neural
stem
cells,
neurons,
oligodendrocytes,
microglia,
astrocytes,
brain
endothelial
cells.
Furthermore,
discusses
understanding
involvement
disorders,
such
as
Alzheimer's
disease,
multiple
sclerosis,
glaucoma,
stroke,
glioma.
Journal of Personalized Medicine,
Год журнала:
2024,
Номер
14(2), С. 170 - 170
Опубликована: Янв. 31, 2024
Postural
orthostatic
tachycardia
syndrome
(POTS)
is
a
common
accompaniment
of
variety
chronic,
inflammatory
diseases,
including
long
COVID,
as
are
small,
insoluble,
'fibrinaloid'
microclots.
We
here
develop
the
argument,
with
accompanying
evidence,
that
fibrinaloid
microclots,
through
their
ability
to
block
flow
blood
microcapillaries
and
thus
cause
tissue
hypoxia,
not
simply
correlated
but
in
fact,
by
preceding
it,
may
be
chief
intermediary
POTS,
which
body's
exaggerated
'physiological'
response
hypoxia.
Similar
reasoning
accounts
for
symptoms
bundled
under
term
'fatigue'.
Amyloids
known
membrane
disruptors,
when
targets
nerve
membranes,
this
can
explain
neurotoxicity
hence
autonomic
nervous
system
dysfunction
contributes
POTS.
Taken
together
view,
we
indicate
microclots
serve
link
POTS
fatigue
COVID
manner
at
once
both
mechanistic
explanatory.
This
has
clear
implications
treatment
such
diseases.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Фев. 13, 2024
Abstract
Amyloid
β
(Aβ)
ion
channels
destabilize
cellular
ionic
homeostasis,
which
contributes
to
neurotoxicity
in
Alzheimer’s
disease.
The
relative
roles
of
various
Aβ
isoforms
are
poorly
understood.
We
use
bilayer
electrophysiology,
AFM
imaging,
circular
dichroism,
FTIR
and
fluorescence
spectroscopy
characterize
channel
activities
four
most
prevalent
peptides,
1-42
,
1-40
their
pyroglutamylated
forms
(AβpE
3-42
AβpE
3-40
)
correlate
them
with
the
peptides’
structural
features.
Solvent-induced
splitting
tyrosine-10
is
discovered
used
assess
sequestration
from
solvent
membrane
insertion.
effectively
embeds
lipid
membranes,
contains
large
fraction
β-sheet
a
β-barrel-like
structure,
multi-subunit
pores
displays
well-defined
In
contrast,
other
peptides
partially
solvent-exposed,
contain
minimal
form
less-ordered
assemblies,
produce
irregular
currents.
These
findings
illuminate
basis
through
permeabilization
may
help
develop
therapies
that
target
Aβ-membrane
interactions.
Chemical Society Reviews,
Год журнала:
2024,
Номер
53(17), С. 8713 - 8763
Опубликована: Янв. 1, 2024
Amyloid
peptides
(AMYs)
and
antimicrobial
(AMPs)
are
considered
as
the
two
distinct
families
of
peptides,
characterized
by
their
unique
sequences,
structures,
biological
functions,
specific
pathological
targets.
However,
accumulating
evidence
has
revealed
intriguing
connections
between
these
peptide
in
context
microbial
infection
neurodegenerative
diseases.
Some
AMYs
AMPs
share
certain
structural
functional
characteristics,
including
ability
to
self-assemble,
presence
β-sheet-rich
membrane-disrupting
mechanisms.
These
shared
features
enable
possess
activity
acquire
amyloidogenic
properties.
Despite
limited
studies
on
AMYs-AMPs
systems,
cross-seeding
phenomenon
emerged
a
crucial
factor
bidirectional
communication
pathogenesis
diseases
host
defense
against
infections.
In
this
review,
we
examine
recent
developments
potential
interplay
AMPs,
well
implications
for
both
infectious
By
discussing
current
progress
challenges
emerging
field,
account
aims
inspire
further
research
investments
enhance
our
understanding
intricate
molecular
crosstalk
AMPs.
This
knowledge
holds
great
promise
development
innovative
therapies
combat
infections
disorders.
Chemical Science,
Год журнала:
2024,
Номер
15(45), С. 18715 - 18750
Опубликована: Янв. 1, 2024
The
construction
of
functional
structures
within
a
single
plane
still
has
lot
challenges.
This
review
article
will
help
us
find
new
groundbreaking
directions
in
lateral
nanoarchitectonics
toward
advanced
material
organization.
ACS Applied Materials & Interfaces,
Год журнала:
2023,
Номер
15(34), С. 40317 - 40329
Опубликована: Авг. 16, 2023
Alzheimer's
disease
(AD)
is
a
major
cause
of
dementia
inducing
memory
loss,
cognitive
decline,
and
mortality
among
the
aging
population.
While
amyloid
aggregation
peptide
Aβ
has
long
been
implicated
in
neurodegeneration
AD,
primarily
through
production
toxic
polymorphic
aggregates
reactive
oxygen
species,
viral
infection
less
explicit
role
etiology
brain
disease.
On
other
hand,
while
COVID-19
pandemic
known
to
harm
human
organs
function,
its
adverse
effects
on
AD
pathobiology
conditions
remain
unclear.
Here
we
first
identified
amyloidogenic
potential
